Vessel wall metabolism and functional activity appear to play an important in maintaining vascular homeostasis. Increasing evidence indicates that direct injury of the endothelial cell, alteration of its production of prostaglandins, or degradation of its basement membrane could result in vascular disease. at present, the factors are responsible for the injury or alternation of endothelial cell function are not will characterized. Intravascular activation of circulating neutrophils or monocytes would result in the formation of a variety of reactive oxygen metabolities which could expose the endothelium to a noxious environment. In this study we will examine the impact of leukocyte-derived oxygen metabolities on three aspects of cultured, human endothelial cell function. First, the ability of oxygen metabolities generated by stimulated leukocytes to alter endothelial cell metabolism or viability will be determined and the specific species responsible for damage identified. The biochemical nature of the injury will be investigated as well as the character and activity of endothelial cell defense mechanisms against oxidant stress. In addition, the capability of injured endothelial cells to recover function will be assessed. Second, the ability of leukocyte-derived oxygen metabolites to impair prostaglandin synthesis or destroy prostaglandin products will be investigated and characterized. Third, we will determine the ability of these oxygen metabolites to degrade purified basement membrane components or intact endothelial cell basement membranes. Finally, we will assess the ability of basement membranes exposed to leukocyte-generated oxidants to support endothelial cell growth. Characterization of the molecular species responsible for vessel wall injury, their mechanism of action and their sites of attack should provide new insight into the pathogenesis of vasculitis, thrombosis and atherosclerosis.